{"doi":"10.1101/2020.02.17.949990","title":"Granulocyte-Colony Stimulating Factor reduces cocaine-seeking and downregulates glutamatergic synaptic proteins in medial prefrontal cortex","abstract":"Abstract Background Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no FDA approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony stimulating factor (G-CSF) as a neuroactive cytokine that alters behavioral response to cocaine, increases synaptic dopamine release, and enhances cognitive flexibility. Here, we investigate the role of G-CSF in affecting extinction and reinstatement of cocaine-seeking and perform detailed characterization of its proteomic effects in multiple limbic substructures. Methods Sprague-Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured. Quantitative assessment of changes in the proteomic landscape in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were performed via data-independent acquisition (DIA) mass spectrometry analysis. Results Administration of G-CSF during extinction accelerated the rate of extinction, and administration during abstinence attenuated cue-induced cocaine-seeking. Analysis of global protein expression demonstrated that G-CSF regulated proteins primarily in mPFC that are critical to glutamate signaling and synapse maintenance. Conclusion Taken together, these findings support G-CSF as a viable translational research target with the potential to reduce drug craving or seeking behaviors. Importantly, recombinant G-CSF exists as an FDA-approved medication which may facilitate rapid clinical translation. Additionally, using cutting-edge multi-region discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123449,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9605,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":377064,"name":"Tanner J. Euston","orcid":"0000-0002-3210-4870","position":1,"is_corresponding":false},{"id":377917,"name":"Rashaun S. Wilson","orcid":null,"position":2,"is_corresponding":false},{"id":377065,"name":"Katherine Meckel","orcid":"0000-0001-8867-201X","position":3,"is_corresponding":false},{"id":377066,"name":"Emily G. Peck","orcid":"0000-0002-2024-8930","position":4,"is_corresponding":false},{"id":377067,"name":"Arthur Godino","orcid":"0000-0002-1732-1498","position":5,"is_corresponding":false},{"id":377918,"name":"Joseph A. Landry","orcid":null,"position":6,"is_corresponding":false},{"id":252441,"name":"Erin S. Calipari","orcid":"0000-0003-4723-0623","position":7,"is_corresponding":false},{"id":271366,"name":"TuKiet T. Lam","orcid":"0000-0002-4850-3462","position":8,"is_corresponding":false},{"id":377068,"name":"Drew D. Kiraly","orcid":"0000-0002-4818-5169","position":9,"is_corresponding":false},{"id":377063,"name":"Rebecca S. Hofford","orcid":"0000-0002-4381-4173","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:59.547352Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}